Reduced Cerebral Blood Flow With Orthostasis Precedes Hypocapnic Hyperpnea, Sympathetic Activation, and Postural Tachycardia Syndrome

Abstract

Hyperventilation, and reduced cerebral blood flow velocity can occur in postural tachycardia syndrome (POTS). We studied orthostatically intolerant patients, with suspected POTS, with a chief complaint of upright dyspnea. Based on our observations of an immediate reduction of cerebral blood flow velocity with orthostasis, we hypothesize that the resulting ischemic hypoxia of the carotid body causes chemoreflex activation, hypocapnic hyperpnea, sympathetic activation, and increased heart rate and blood pressure in this subset of POTS. We compared 11 dyspneic POTS subjects to 10 healthy controls during a 70° head-up tilt. In POTS subjects during initial orthostasis prior to BP recovery; central blood volume and mean arterial pressure were reduced (P<0.025) resulting in a significant (P<0.001) decrease in cerebral blood flow velocity, which temporally preceded (17±6 s; P<0.025) a progressive increase in minute ventilation and decrease in end tidal CO2 (P<0.05), compared to controls. Sympathoexcitation, measured by muscle sympathetic nerve activity, was increased in POTS, (P<0.01), and inversely proportional to end tidal CO2 and resulted in an increase in heart rate, (P<0.001), total peripheral resistance (P<0.025), and a decrease in cardiac output (P<0.025). The decrease in cerebral blood flow velocity and mean arterial pressure during initial orthostasis was greater (P<0.025) in POTS. Our data suggest that exaggerated initial central hypovolemia during initial orthostatic hypotension in POTS results in reduced cerebral blood flow velocity and postural hypocapnic hyperpnea that perpetuates cerebral ischemia. We hypothesize that sustained hypocapnia and cerebral ischemia produce sympathoexcitation, tachycardia and a statistically significant increase in blood pressure.

Postural Hyperventilation as a Cause of Postural Tachycardia Syndrome: Increased Systemic Vascular Resistance and Decreased Cardiac Output When Upright in All Postural Tachycardia Syndrome Variants

“…Nevertheless, intermittent hyperventilation, presenting as postural hypocapnic hyperpnea, has been reported 14, 15, 16, 17. We observed hypocapnic hyperpnea in POTS in response to a rapid initial orthostatic decrease in CO and CBV 15.…”

“…The carotid body is primarily responsible for sensing “stagnant ischemia” or “ischemic hypoxia” in conditions of reduced CBV and CO 12. We have previously shown markedly increased sympathetic nerve activity in these patients 15. We propose that chemoreflex‐mediated sympathoexcitation contributes importantly to vasoconstriction and increased BP while further restricting CO in these patients.…”

“…The relationship of hyperventilation to orthostasis has been revived by recent reports from our laboratory14, 15 and a report from the Mayo autonomic group,17 contemporary with the definition of POTS 3. More recently, “hyperventilation syndrome” (but not “postural hyperventilation”) has been subsumed under the aegis of “dysfunctional breathing” treated with variable success by breathing retraining 42…”

“…For that reason, the first minute of tilt is often not used for analysis. However, our prior data showed that this time period may be critical to initiating hypocapnic hyperpnea 15. Therefore, we retained all early physiological measurements following tilt, and graphically displayed the nadir for BP, CO, and CBV and the zenith for HR and SVR during this early tilt epoch, which is designated as “initial.” Thereafter, upright measurements were divided into 5 additional stages of “early” (2–4 minutes), “middle” (4–6 minutes), “late” (6–8 minutes), “end” (8–10 minutes), and “CO 2 .” Only hyperventilating patients with POTS received CO 2 , and this additional epoch denoted CO 2 is included in the graphic results.…”

Managing the patient with episodic sinus tachycardia and orthostatic intolerance

“…Up to 50% of cases have an antecedent viral illness, and 25% have a family history of similar complaints [9,10]. The primary mechanism is venous pooling and central hypovolemia during upright posture, resulting in secondary sympathetic excitation that perpetuates the tachycardic response [21,22]. Autoimmunity may exert an effect; elevated alpha-1 receptor partial antagonist and beta-1 receptor, beta-2 receptor agonist autoantibodies were identified in the serum of POTS patients [23].…”